Project Summary/Abstract There has been rapid escalation of type 2 diabetes (T2D) rates in adolescents. Early-onset T2D (<20y) typically shows a more aggressive course than adult-onset T2D and disproportionately affects girls from disadvantaged, racial/ethnic groups. This group of girls also is at heightened risk for depression, and depression and T2D are linked. Depressive symptoms often manifest in adolescence and are a prospective risk factor for worsening of insulin sensitivity, the major physiological precursor?in combination with deterioration of pancreatic ?-cell ca- pacity to secrete insulin?in the path to T2D. The effects of depression on poor insulin sensitivity remain even after accounting for adiposity. In theory, depressive symptoms may worsen insulin sensitivity through stress- induced behaviors (e.g., disinhibited eating, [physical inactivity], sleep disturbance) and stress-induced phys- iological causal mechanisms (e.g., hypercortisolism). The central theme of our proposal is that intervening to reduce depressive symptoms in adolescents at-risk for T2D may offer an innovative, targeted approach to ame- liorate insulin resistance and to, consequently, preserve ?-cell function and lessen T2D risk. In preliminary data from an NIH K99/R00 Award, the PI found initial evidence that a 6-week cognitive-behavioral group decreased depressive symptoms and prevented worsening of insulin sensitivity 1 year later in overweight and obese girls with moderate depressive symptoms and a family history of T2D, in comparison to a 6-week health education control group. Directly extending these findings, the aims of this R01 proposal are: 1) to assess the efficacy of a 6-week cognitive-behavioral depression group vs. a 6-week health education control group for improving insulin sensitivity and preserving ?-cell function in racially/ethnically diverse adolescent girls at-risk for T2D with mod- erate depressive symptoms over a 1-year follow-up; 2) to evaluate changes in eating, [physical activity], and sleep as behavioral explanatory mediators underlying the relationship between decreases in depressive symp- toms and improvements in insulin sensitivity and ?-cell function over 1 year and 3) to test changes in cortisol awakening response, diurnal cortisol rhythm, and total daily cortisol output as physiological mechanisms explain- ing the relationship between decreases in depressive symptoms and improvements in insulin sensitivity and ?- cell function over 1 year. We have assembled a strong, multidisciplinary team of scientists with expertise in depression, obesity, eating (PI: Lauren Shomaker, PhD), [child and adolescent insulin sensitivity and secre- tion] (Co-I: Kristen Nadeau, MD, MS), [puberty, precursors of early-onset T2D] (Co-I: Megan Kelsey, MD, MS), and statistics (Co-I: Sangeeta Rao, PhD), as well as consultation from experts on [ambulatory physical activity monitoring (Andrea Kriska, PhD, MS)], sleep medicine (Kenneth Wright Jr, PhD), [and adolescent depression (Eric Stice, PhD)]. Our long-term goal is to identify feasible, cost-effective public health solutions that have high potential for effective dissemination in communities at-risk for cardiometabolic disease and to understand the mechanisms by which alleviating psychosocial stress facilitates more positive health outcomes.